Effects of L-carnitine against oxidative stress in human hepatocytes: involvement of peroxisome proliferator-activated receptor alpha

<p>Abstract</p> <p>Background</p> <p>Excessive oxidative stress and lipid peroxidation have been demonstrated to play important roles in the production of liver damage. L-carnitine is a natural substance and acts as a carrier for fatty acids across the inner mitochondrial membrane for subsequent beta-oxidation. It is also an antioxidant that reduces metabolic stress in the cells. Recent years L-carnitine has been proposed for treatment of various kinds of disease, including liver injury. This study was conducted to evaluate the protective effect of L-carnitine against hydrogen peroxide (H₂O₂)-induced cytotoxicity in a normal human hepatocyte cell line, HL7702.</p> <p>Methods</p> <p>We analyzed cytotoxicity using MTT assay and lactate dehydrogenase (LDH) release. Antioxidant activity and lipid peroxidation were estimated by reactive oxygen species (ROS) levels, activities and protein expressions of superoxide dismutase (SOD) and catalase (CAT), and malondialdehyde (MDA) formation. Expressions of peroxisome proliferator-activated receptor (PPAR)-alpha and its target genes were evaluated by RT-PCR or western blotting. The role of PPAR-alpha in L-carnitine-enhanced expression of SOD and CAT was also explored. Statistical analysis was performed by a one-way analysis of variance, and its significance was assessed by Dennett's post-hoc test.</p> <p>Results</p> <p>The results showed that L-carnitine protected HL7702 cells against cytotoxity induced by H₂O₂. This protection was related to the scavenging of ROS, the promotion of SOD and CAT activity and expression, and the prevention of lipid peroxidation in cultured HL7702 cells. The decreased expressions of PPAR-alpha, carnitine palmitoyl transferase 1 (CPT1) and acyl-CoA oxidase (ACOX) induced by H₂O₂can be attenuated by L-carnitine. Besides, we also found that the promotion of SOD and CAT protein expression induced by L-carnitine was blocked by PPAR-alpha inhibitor MK886.</p> <p>Conclusions</p> <p>Taken together, our findings suggest that L-carnitine could protect HL7702 cells against oxidative stress through the antioxidative effect and the regulation of PPAR-alpha also play an important part in the protective effect.</p

Quantum Alternating Operator Ansatz for Solving the Minimum Exact Cover Problem

The minimum exact cover (MEC) is a common combinatorial optimization problem, with wide applications in tail-assignment and vehicle routing. In this paper, we adopt quantum alternating operator ansatz (QAOA+) to solve MEC problem. In detail, to obtain a trivial feasible solution, we first transform MEC into a constrained optimization problem with two objective functions. Then, we adopt the linear weighted sum method to solve the above constrained optimization problem and construct the corresponding target Hamiltonian. Finally, to improve the performance of this algorithm, we adopt parameters fixing strategy to simulate, where the experimental instances are 6, 8, and 10 qubits. The numerical results show that the solution can be obtained with high probability when level $p$ of the algorithm is low. Besides, we optimize the quantum circuit by removing single-qubit rotating gates $R_Z$. We found that the number of quantum gates is reduced by $np$ for $p$-level optimized circuit. Furthermore, $p$-level optimized circuit only needs $p$ parameters, which can achieve an experimental effect similar to original circuit with $2p$ parameters

Identification and pharmacokinetics of saponins in Rhizoma Anemarrhenae after oral administration to rats by HPLC-Q-TOF/MS and HPLC-MS/MS

Rhizoma Anemarrhenae is a well-known herbal medicine with saponins as its commonly regarded major bioactive components. It is essential to classify the properties of saponins which are associated with their toxicity and efficacy. In this study, 25 compounds were identified by HPLC-Q-TOF/MS in the extract of Rhizoma Anemarrhenae and 8 saponins were detected in rat plasma by HPLC-MS/MS after oral administration of this extract. These were neomangiferin, mangiferin, timosaponin E1, timosaponin E, timosaponin B-II, timosaponin B-III, timosaponin A-III and timosaponin A-I. A sensitive and accurate HPLC-MS/MS method was developed and successfully applied to a pharmacokinetic study of the abovementioned eight saponins after oral administration of the Rhizoma Anemarrhenae extract to rats. The method validation, including specificity, linearity, precision, accuracy, recovery, matrix effect and robustness, met the requirements of the intended use. The pharmacokinetic parameter, Tmax value, ranged from 2 to 8 h for these eight saponins whereas their elimination half-life (t1/2) ranged from 4.06 to 9.77 h, indicating slow excretion. The plasma concentrations of these eight saponins were all very low, indicating a relatively low oral bioavailability. All these results provide support for further clinical studies

3-Ethyl 5-methyl 4-(2,3-dichloro­phen­yl)-2,6-dimethyl­pyridine-3,5-dicarboxyl­ate

In the title compound, C18H17Cl2NO4, an oxidation product of felodipine, the dihedral angle between the benzene and pyridine rings is 75.3 (4)°. The crystal structure is stabilized by intermolecular C—H⋯O interactions

Variational quantum algorithm-preserving feasible space for solving the uncapacitated facility location problem

The Quantum Alternating Operator Ansatz (QAOA+) is one of the Variational Quantum Algorithm (VQA) specifically developed to tackle combinatorial optimization problems by exploring the feasible space in search of a target solution. For constrained optimization problems with unconstrained variables, which we call Unconstrained-Variables Problems (UVPs), the mixed operators in the QAOA+ circuit are applied to the constrained variables, while the single-qubit rotating gates $R_X$ operate on the unconstrained variables. The expressibility of this circuit is limited by the shortage of two-qubit gates and the parameter sharing in the $R_X$, which consequently impacts the performance of QAOA+ for solving UVPs. Therefore, it is crucial to develop a suitable ansatz for UVPs. In this paper, we propose the Variational Quantum Algorithm-Preserving Feasible Space (VQA-PFS) ansatz, exemplified by the Uncapacitated Facility Location Problem (UFLP), that applies mixed operators on constrained variables while employing Hardware-Efficient Ansatz (HEA) on unconstrained variables. The numerical results demonstrate that VQA-PFS significantly enhances the success probability and exhibits faster convergence compared to QAOA+, Quantum Approximation Optimization Algorithm (QAOA), and HEA. Furthermore, VQA-PFS reduces the circuit depth dramatically in comparison to QAOA+ and QAOA. Our algorithm is general and instructive in tackling UVPs